rs1927350

Variant names:

• chr13-110466199-T-G
• rs1927350
• NM_001846.4:c.2038+137T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.2038+137T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 988,302 control chromosomes in the GnomAD database, including 170,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27927 hom., cov: 33)
  • Exomes 𝑓: 0.57 (142404 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.997
• Publications: 3 publications found

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

COL4A2 Gene-Disease associations (from GenCC):

• porencephaly 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• COL4A1 or COL4A2-related cerebral small vessel disease

  Inheritance: AD Classification: MODERATE Submitted by: Illumina
• familial porencephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 13-110466199-T-G is Benign according to our data. Variant chr13-110466199-T-G is described in ClinVar as Benign. ClinVar VariationId is 1273943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2038+137T>G		intron_variant	Intron 26 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2038+137T>G		intron_variant	Intron 26 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90568 AN: 152028 Hom.: 27894 Cov.: 33

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.574 AC: 479656 AN: 836156 Hom.: 142404 AF XY: 0.571 AC XY: 238722 AN XY: 417812

African (AFR) AF: 0.721 AC: 14510 AN: 20120

American (AMR) AF: 0.434 AC: 10261 AN: 23648

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 10494 AN: 16174

East Asian (EAS) AF: 0.251 AC: 8139 AN: 32462

South Asian (SAS) AF: 0.475 AC: 23219 AN: 48902

European-Finnish (FIN) AF: 0.443 AC: 18873 AN: 42634

Middle Eastern (MID) AF: 0.684 AC: 2973 AN: 4346

European-Non Finnish (NFE) AF: 0.605 AC: 368998 AN: 609626

Other (OTH) AF: 0.580 AC: 22189 AN: 38244

GnomAD4 genome AF: 0.596 AC: 90660 AN: 152146 Hom.: 27927 Cov.: 33 AF XY: 0.583 AC XY: 43368 AN XY: 74372

African (AFR) AF: 0.709 AC: 29443 AN: 41508

American (AMR) AF: 0.502 AC: 7670 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2328 AN: 3472

East Asian (EAS) AF: 0.294 AC: 1520 AN: 5170

South Asian (SAS) AF: 0.461 AC: 2224 AN: 4824

European-Finnish (FIN) AF: 0.428 AC: 4534 AN: 10582

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40846 AN: 67986

Other (OTH) AF: 0.598 AC: 1265 AN: 2114

Alfa AF: 0.611 Hom.: 3711

Bravo AF: 0.606

Asia WGS AF: 0.405 AC: 1409 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1927350; hg19: chr13-111118546; COSMIC: COSV64625577; COSMIC: COSV64625577;